The overarching mission of the Yale Older Americans Independence Center (OAIC), established in 1992, is to provide intellectual leadership and innovation for aging research that is directed at enhancing the independence of older persons. The unifying theme of the Yale OAIC remains the investigation of multifactorial geriatric conditions, encompassing single conditions resulting from multiple contributing factors or affecting multiple outcome domains and multiple conditions occurring simultaneously. The central Yale OAIC hypothesis is that geriatric conditions are determined by the co-occurrence of multiple predisposing and precipitating factors. These conditions and factors, in turn, affect a range of health outcomes. The predisposing factors may be at the genetic, molecular, physiologic, impairment, disease, or socio-demographic level, while the precipitating factors may be behavioral, environmental, social, medical, or psychological. The Yale OAIC theme requires designs and models (e.g. molecular, animal, and statistical) that inform the study of multiple, simultaneously interactive factors and outcomes. As a prominent subtheme, the Yale OAIC also aims to advance the science of clinical decision making in the face of trade-offs and multiple competing outcomes. This includes developing strategies to elicit older persons? health outcome priorities. The Specific Aims of the Yale OAIC are to: 1) foster the career development of future academic leaders, from multiple disciplines, in aging research; 2) train investigators, biostatisticians and other methodologists in the skills necessary to design, conduct, analyze, and disseminate findings from studies of multifactorial geriatric conditions; 3) develop and disseminate design and analytic techniques for conducting studies of multifactorial geriatric conditions; 4) develop strategies for recruiting into, and retaining, a broad spectrum of older persons, including minorities, into studies of multifactorial geriatric conditions; 5) investigate the causative mechanisms of, and develop and test effective treatments for, geriatric conditions from a multifactorial research perspective; 6) develop strategies to enhance clinical decision making in the setting of multiple competing outcomes; 7) encourage and facilitate interdisciplinary research (basic, translational and clinical) that connects to our focus on multifactorial geriatric conditions; and 8) further strengthen collaborations with other OAICs. The Yale OAIC cores include: 1) Leadership and Administrative; 2) Research Education; 3) Pilot/Exploratory Studies; 4) Operations; and 5) Biostatistics. For the first one to two years of the next cycle, we propose to support 3 Pepper Scholars, 3 pilot studies, 2 development projects, and 29 externally funded projects. The Yale OAIC has made outstanding progress during the current funding cycle, as evidenced by publication of 411 manuscripts (with an additional 23 submitted) and receipt of more than $178 million in grants (total costs), with an additional $16.3 million pending. Based on grants received, the return on investment from OAIC support is more than 20 to 1.